Mammalian cells that have undergone malignant transformation, that is, are "cancerous", bear chemical markers that potentially allow recognition by the host's own immune system. Nevertheless, the host's immune system frequently fails to recognize and/or eliminate cancer cells. Despite chemotherapy and/or surgery, the cancer may kill the host.
Attempts have been made to enhance the immune system's natural antitumor potential by various immunotherapy treatments. Immunotherapies are typically used in conjunction with surgery and/or chemotherapy. Certain immunotherapies involve administering biological. response modifiers including, for example: tumor necrosis factor (hereinafter "TNF"), which includes two closely related molecular species TNF-.beta., also known as lymphotoxin, and TNF-.alpha., also known as cachectin, which directly kill certain types of tumor cells; -interferon which activates T cells, natural killer cells and inhibits the growth of certain tumor cells; and .alpha.-interleukin-2, which increases the proliferation of antigen specific cytotoxic T-cells, B cells, natural killer cells and activates lymphokine-activated killer cells. Interleukin-2 has demonstrated limited effectiveness alone even at high dosages. However, interleukin-2 treatment is toxic to the patient, and is currently recommended only for patients for whom no other treatment is available.
TNF-.beta., produced by activated macrophages and lymphocytes, is a potent mediator of natural killer cells, lymphokine-activated killer cells and cytotoxic lymphocyte activity. In addition, TNF is cytotoxic and cytostatic to tumor cells. Several cytokines interact synergistically with TNF. Administration of TNF has prolonged the survival of leukemia patients, resulted in the regression of various solid tumors and demonstrated potential efficacy in the treatment of various cancers such as bladder and gastrointestinal cancer. While interleukin 2 and TNF show promise in the treatment of cancer, they are relatively non-specific effector cytokines with a wide range of activities, some of which cause undesirable toxic side effects at therapeutic doses.
A problem with administering biological response modifiers is that the modifier, particularly when given in high continuous doses, is expensive, may require multiple treatments, may produce only marginal results and has toxic side effects.
Other immunotherapy methods involve the removal and manipulation of host cells or fluids. Removal of peripheral blood cells and treatment with interleukin-2 has increased their tumoricidal capability by stimulating the activity of natural killer cells and lymphokine activated killer cells. Immunodepletive therapy of patient's plasma and bone marrow has been employed to remove blocking factors or to add tumoricidal factors. However, these treatments are time consuming, complex, costly and often ineffective. As with administration of interleukin-2 and TNF, there are serious toxic effects in many patients.
Passive immunotherapy using monoclonal antibodies, directed to cancer cell antigens, has been employed to initiate cancer cell destruction via the host's immune system and offers great potential in the treatment of cancer. However, the promise of monoclonal antibodies depends upon their binding to a unique antigen on the surface of the cancer cell. It is rare that these cell surface antigens or epitopes thereof are unique to the cancer cell. In addition, low surface density of the cancer cell surface antigen, low affinity of the monoclonal antibody for the antigen and poor antibody uptake by the cancer cell are serious problems. Partially for these reasons, no therapy with simple monoclonal antibody has ever caused tumor regression. The most successful monoclonal antibody treatments depend on conjugating the antibody with a cytotoxic drug or radioisotope. While treatments such as these show considerable promise, there are still toxic side effects.
To date no single treatment cures cancer, and thus it is desirable to increase the immunotherapy arsenal against cancer. It is particularly desirable to have a low cost, less toxic, anti-cancer immunotherapy which enhances the host's immune system ability to destroy or contain cancer.
In addition to treating cancers it is also desirable to have a noninvasive diagnostic test that detects the presence of cancer. Currently cancer is detected primarily by imaging techniques such as x-ray, CAT scan and NMR.
CAT scan and NMR procedures are moderately expensive and are typically employed when the patient's symptoms warrant an investigation into the cause. Thus, where a patient is asymptomatic a cancer may grow undetected.
While chest x-rays may be used fairly routinely to diagnose lung cancer and mammograms have been recommended in some cases, the x-ray is limited in scope and will not alert a physician to the presence of other cancers. Moreover, x-rays expose a patient to radiation which is carcinogenic and are thus used only in subjects at high risk for cancer.
It would be desirable to have a general inexpensive routine diagnostic test for cancer that does not employ radiation which is capable of detecting the presence of cancer and thereby alerting the physician and patient to the need for further examination.